Multi-modal image confidence: a novel method for tumor and organ boundary representation.

BACKGROUND: The ambiguous boundaries of tumors and organs at risk (OARs) seen in medical images pose challenges in treatment planning and other tasks in radiotherapy. METHODS: This study introduces an innovative analytical algorithm, Multi-Modal Image Confidence (MMC), which exploits the collective strengths of complementary multi-modal medical images to determine a confidence measure for each voxel belonging to the region of interest (ROI). MMC facilitates the creation of modality-specific ROI-enhanced images, enabling a detailed representation of the ROI's boundaries and internal features. By employing an interpretable mathematical model that propagates voxel confidence based on inter-voxel correlations, MMC avoids the need for model training, distinguishing it from deep learning (DL)-based methods. RESULTS: The performance of the proposed algorithm was qualitatively and quantitatively evaluated using 156 nasopharyngeal carcinoma cases and 1251 glioma cases. Qualitative assessments underscored the accuracy of MMC and ROI-enhanced images in estimating lesion boundaries and capturing internal tumor characteristics. Quantitative analyses revealed strong agreement between MMC and manual delineations. CONCLUSION: This paper introduces a novel analytical algorithm to identify and depict ROI boundaries based on complementary multi-modal 3D medical images. The applicability of the proposed method can extend to both targets and OARs at diverse anatomical sites across multiple image modalities, amplifying its potential for augmenting radiotherapy-related tasks.

ENAH transcriptionally activated by YY1 promotes growth and invasion of laryngocarcinoma cells through PI3K/AKT signaling.

BACKGROUND: Laryngocarcinoma is a common malignancy in the upper respiratory tract. Enabled homolog (ENAH) is an actin-binding protein that is associated with the development of various cancers. However, its role and mechanism in laryngocarcinoma remain unknown. METHODS: The ENAH level in laryngocarcinoma was examined in silico, in vitro and in vivo. The prognostic analysis of the ENAH level was assessed on laryngocarcinoma patients. Gain- and loss-of-function assays were conducted in AMC-HN-8 and TU686 cells. Sh-ENAH-containing AMC-HN-8 cells were implanted into naked mice. The role and mechanism of ENAH in laryngocarcinoma were investigated by CCK-8, transwell, immunofluorescence, dual luciferase, RT-qPCR, immunohistochemistry, and western blotting experiments. RESULTS: The ENAH level was upregulated in laryngocarcinoma, which predicted a poor prognosis in laryngocarcinoma patients. Gain- and loss-of-function results showed that ENAH promoted proliferation, invasion and EMT of laryngocarcinoma cells. Moreover, ENAH was transcriptionally activated by YY1, and YY1/ENAH axis enhanced these malignant progresses of laryngocarcinoma cells. Besides, ENAH activated the PI3K/AKT pathway, and 740Y-P abolished the accelerative role of ENAH in proliferation, invasion and EMT of laryngocarcinoma cells. Furthermore, knockdown of ENAH reduced tumor size and weight, and the expression level of vimentin and PI3K/AKT pathway in tumor-bearing mice. CONCLUSION: ENAH transcriptionally activated by YY1 promotes cell growth, invasion and EMT of laryngocarcinoma through the activation of PI3K/AKT signaling.

lncRNA FLJ20021 regulates CDK1-mediated PANoptosis in a ZBP1-dependent manner to increase the sensitivity of laryngeal cancer-resistant cells to cisplatin.

In this study, we investigated the role of the newly discovered lncRNA FLJ20021 in laryngeal cancer (LC) and its resistance to cisplatin treatment. We initially observed elevated lncRNA FLJ20021 levels in cisplatin-resistant LC cells (Hep-2/R). To explore its function, we transfected lncRNA FLJ20021 and cyclin-dependent kinase 1 (CDK1) into Hep-2/R cells, assessing their impact on cisplatin sensitivity and PANoptosis. Silencing lncRNA FLJ20021 effectively reduced cisplatin resistance and induced PANoptosis in Hep-2/R cells. Mechanistically, lncRNA FLJ20021 primarily localized in the nucleus and interacted with CDK1 mRNA, thereby enhancing its transcriptional stability. CDK1, in turn, promoted panapoptosis in a ZBP1-dependent manner, which helped overcome cisplatin resistance in Hep-2/R cells. This study suggests that targeting lncRNA FLJ20021 can be a promising approach to combat cisplatin resistance in laryngeal cancer by regulating CDK1 and promoting PANoptosis via the ZBP1 pathway. These findings open up possibilities for lncRNA-based therapies in the context of laryngeal cancer.

Correlation of acoustic voice analysis and Voice Handicap Index in patients with postoperative unilateral vocal cord paralysis after thyroid surgery.

Unilateral vocal cord paralysis is frequently observed in patients who undergo thyroid surgery. This study explored the correlation between acoustic voice analysis (objective measure) and Voice Handicap Index (VHI, a self-assessment tool). One hundred and forty patients who had thyroid surgery with or without postoperative unilateral vocal cord paralysis (PVCP and NPVCP) were included. The patients were evaluated by the VHI and Dysphonia Severity Index (DSI) tools. VHI scores were significantly higher in PVCP patients than in NPVCP patients. Jitter (%) and shimmer (%) were significantly increased, whereas DSI was significantly decreased in PVCP patients. Receiver operating characteristics curve revealed that VHI scores were associated with the diagnosis of PVCP, of which VHI total score yielded an area under the curve (AUC) of 0.81. Among acoustic parameters, DSI was highly associated to PVCP (AUC=0.82, 95%CI=0.75 to 0.89). Moreover, we found a correlation between VHI scores and voice acoustic parameters. Among them, DSI had a moderate correlation with functional and VHI scores, as suggested by an R value of 0.41 and 0.49, respectively. VHI scores and acoustic parameters were associated with the diagnosis of PVCP.

Vaginal flora in HPV infection: a cross­sectional analysis.

OBJECTIVE: The vaginal flora has been reported to be associated with human papillomavirus (HPV) infection. The purpose of this study was to investigate the characteristics of the cervical microbiota in patients with HPV infection and to analyse the changes in the vaginal flora and enzyme profiles in females with HPV infection. METHODS: We conducted a cross-sectional study involving 206 participants who underwent HPV genotyping, sexually transmitted diseases pathogen testing, cytology examination, and microbiome analysis. Additionally, we collected 115 HPV-negative samples and 48 HPV-positive samples for 16S rRNA amplicon sequencing. The vaginal microbial communities of both groups were analysed for diversity and differences to explore their association with HPV infection. RESULTS: The abundance of Lactobacillus was found to be reduced, while Gardnerella vaginalis was significantly more prevalent in the HPV + group. In terms of alpha diversity indices, the Shannon index (P = .0036) and Simpson index (P = .02) were higher in the HPV + group compared to the HPV - group, indicating greater community diversity in the HPV + group. Among the 10 sexually transmitted diseases pathogens analysed, Uup3 and Uup6 were significantly associated with HPV infection. Statistically significant differences were observed in Nugent scores and bacterial vaginosis between the two groups (P < .05). In functional analysis, 11 proteins and 13 enzymes were found to be significantly altered in the HPV + group. CONCLUSION: Our study demonstrates that disruptions in the vaginal flora are associated with HPV infection. Reduced levels of Lactobacillus, increased prevalence of Gardnerella, and abnormal enzyme profiles are closely linked to HPV infection.

The purpose of this study was to investigate the characteristics of the cervical microbiota in patients with human papillomavirus infection and to analyse the changes in the vaginal flora and enzyme profiles in females with human papillomavirus infection. We conducted a cross-sectional study involving 206 participants who underwent human papillomavirus genotyping, sexually transmitted diseases pathogen testing, cytology examination, and microbiome analysis. Additionally, we collected 115 HPV-negative samples and 48 HPV-positive samples for 16S rRNA amplicon sequencing. The abundance of Lactobacillus was found to be reduced, while Gardnerella vaginalis was significantly more prevalent in the HPV + group. In functional analysis, 11 proteins and 13 enzymes were found to be significantly altered in the HPV + group. Our study demonstrates that disruptions in the vaginal flora are associated with HPV infection. Reduced levels of Lactobacillus, increased prevalence of Gardnerella, and abnormal enzyme profiles are closely linked to HPV infection.

The later-line efficacy and safety of immune checkpoint inhibitors plus anlotinib in EGFR-mutant patients with EGFR-TKI-resistant NSCLC: a single-center retrospective study.

BACKGROUND: Effective treatment after EGFR-TKI resistance is of great clinical concern. We aimed to investigate the efficacy and safety of anlotinib in combination with an anti-PD-1/PD-L1 antibody in later-line therapy for EGFR-mutant NSCLC patients after TKI treatment failure and to explore the independent predictive factors of therapeutic efficacy. METHODS: A total of 71 patients with confirmed advanced EGFR-mutated NSCLC who progressed after previous standard EGFR-TKI therapy but still failed after multiline treatments were included retrospectively in this study. Most of the patients had previously received at least three lines of treatment. All were treated with anlotinib combined with anti-PD-1 or anti-PD-L1 therapy. The safety of this combined treatment was assessed by the incidence of adverse events. The efficacy of the regimens was evaluated by survival analysis (OS, PFS, ORR, DCR). RESULTS: The median follow-up period was 28.6 months (range: 2.3-54.0 months), and the median number of treatment lines was 4. The overall response rate (ORR) and disease control rate (DCR) were 19.7% and 77.5%, respectively. The median PFS was 5.8 months (95% CI 4.2-7.4 months), and the median OS was 17.1 months (95% CI 12.0-22.3 months). Patients who received immune checkpoint inhibitors plus anlotinib had an encouraging intracranial ORR of 38.5% and a DCR of 80.8%. ECOG performance status < 2 at baseline was independent protective factors of PFS. Metastatic organs and ECOG performance status were independent parameters in predicting OS. Treatment-related adverse events occurred in 66 (93.0%) patients; most of the adverse events were Grade 1-2, and no increase in adverse events was observed compared to monotherapy. CONCLUSION: Anlotinib combined with an anti-PD-1/PD-L1-based regimen exhibited promising efficacy and tolerance in NSCLC patients with EGFR mutations after previous TKI failure. The efficacy of this combined regimen in patients with EGFR mutations should be further evaluated.

The application of different machine learning models based on PET/CT images and EGFR in predicting brain metastasis of adenocarcinoma of the lung.

OBJECTIVE: To explore the value of six machine learning models based on PET/CT radiomics combined with EGFR in predicting brain metastases of lung adenocarcinoma. METHODS: Retrospectively collected 204 patients with lung adenocarcinoma who underwent PET/CT examination and EGFR gene detection before treatment from Cancer Hospital Affiliated to Shandong First Medical University in 2020. Using univariate analysis and multivariate logistic regression analysis to find the independent risk factors for brain metastasis. Based on PET/CT imaging combined with EGFR and PET metabolic indexes, established six machine learning models to predict brain metastases of lung adenocarcinoma. Finally, using ten-fold cross-validation to evaluate the predictive effectiveness. RESULTS: In univariate analysis, patients with N2-3, EGFR mutation-positive, LYM%≤20, and elevated tumor markers(P<0.05) were more likely to develop brain metastases. In multivariate Logistic regression analysis, PET metabolic indices revealed that SUVmax, SUVpeak, Volume, and TLG were risk factors for lung adenocarcinoma brain metastasis(P<0.05). The SVM model was the most efficient predictor of brain metastasis with an AUC of 0.82 (PET/CT group),0.70 (CT group),0.76 (PET group). CONCLUSIONS: Radiomics combined with EGFR machine learning model as a new method have higher accuracy than EGFR mutation alone. SVM model is the most effective method for predicting brain metastases of lung adenocarcinoma, and the prediction efficiency of PET/CT group is better than PET group and CT group.

Phase I/II clinical trial of efficacy and safety of EGCG oxygen nebulization inhalation in the treatment of COVID-19 pneumonia patients with cancer.

BACKGROUND: The antiviral drug Nirmatrelvir was found to be a key drug in controlling the progression of pneumonia during the infectious phase of COVID-19. However, there are very few options for effective treatment for cancer patients who have viral pneumonia. Glucocorticoids is one of the effective means to control pneumonia, but there are many adverse events. EGCG is a natural low toxic compound with anti-inflammatory function. Thus, this study was designed to investigate the safety and efficacy of epigallocatechin-3-gallate (EGCG) aerosol to control COVID-19 pneumonia in cancer populations. METHODS: The study was designed as a prospective, single-arm, open-label phase I/II trial at Shandong Cancer Hospital and Institute, between January 5, 2023 to March 31,2023 with viral pneumonia on radiographic signs after confirmed novel coronavirus infection. These patients were treated with EGCG nebulization 10 ml three times daily for at least seven days. EGCG concentrations were increased from 1760-8817umol/L to 4 levels with dose escalation following a standard Phase I design of 3-6 patients per level. Any grade adverse event caused by EGCG was considered a dose-limiting toxicity (DLT). The maximum tolerated dose (MTD) is defined as the highest dose with less than one-third of patients experiencing dose limiting toxicity (DLT) due to EGCG. The primary end points were the toxicity of EGCG and CT findings, and the former was graded by Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0. The secondary end point was the laboratory parameters before and after treatment. RESULT: A total of 60 patients with high risk factors for severe COVID-19 pneumonia (factors such as old age, smoking and combined complications)were included in this phase I-II study. The 54 patients in the final analysis were pathologically confirmed to have tumor burden and completed the whole course of treatment. A patient with bucking at a level of 1760 umol/L and no acute toxicity associated with EGCG has been reported at the second or third dose gradients. At dose escalation to 8817umol/L, Grade 1 adverse events of nausea and stomach discomfort occurred in two patients, which resolved spontaneously within 1 hour. After one week of treatment, CT showed that the incidence of non-progression of pneumonia was 82% (32/39), and the improvement rate of pneumonia was 56.4% (22/39). There was no significant difference in inflammation-related laboratory parameters (white blood cell count, lymphocyte count, IL-6, ferritin, C-reactive protein and lactate dehydrogenase) before and after treatment. CONCLUSION: Aerosol inhalation of EGCG is well tolerated, and preliminary investigation in cancer population suggests that EGCG may be effective in COVID-19-induced pneumonia, which can promote the improvement of patients with moderate pneumonia or prevent them from developing into severe pneumonia. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05758571. Date of registration: 8 February 2023.

Correlation of acoustic voice analysis and Voice Handicap Index in patients with postoperative unilateral vocal cord paralysis after thyroid surgery

Unilateral vocal cord paralysis is frequently observed in patients who undergo thyroid surgery. This study explored the correlation between acoustic voice analysis (objective measure) and Voice Handicap Index (VHI, a self-assessment tool). One hundred and forty patients who had thyroid surgery with or without postoperative unilateral vocal cord paralysis (PVCP and NPVCP) were included. The patients were evaluated by the VHI and Dysphonia Severity Index (DSI) tools. VHI scores were significantly higher in PVCP patients than in NPVCP patients. Jitter (%) and shimmer (%) were significantly increased, whereas DSI was significantly decreased in PVCP patients. Receiver operating characteristics curve revealed that VHI scores were associated with the diagnosis of PVCP, of which VHI total score yielded an area under the curve (AUC) of 0.81. Among acoustic parameters, DSI was highly associated to PVCP (AUC=0.82, 95%CI=0.75 to 0.89). Moreover, we found a correlation between VHI scores and voice acoustic parameters. Among them, DSI had a moderate correlation with functional and VHI scores, as suggested by an R value of 0.41 and 0.49, respectively. VHI scores and acoustic parameters were associated with the diagnosis of PVCP.

Coronary Artery Calcium and Cognitive Decline in the Diabetes Prevention Program Outcomes Study.

Background Our aim was to investigate the association of coronary artery calcium (CAC) with cognitive function in adults with impaired glucose tolerance or type 2 diabetes. Methods and Results The Diabetes Prevention Program was a randomized controlled trial comparing an intensive lifestyle intervention, metformin, or placebo for prevention of type 2 diabetes among patients with prediabetes. After 3 years, intensive lifestyle intervention and placebo were stopped, the metformin arm was unmasked, and participants continued in the DPPOS (Diabetes Prevention Program Outcomes Study). Approximately 14 years after randomization (Y14), CAC (Agatston score) was assessed with computed tomography, and cognitive performance was assessed with the Spanish English Verbal Learning Test (SEVLT) and Digit Symbol Substitution Test. SEVLT and Digit Symbol Substitution Test were reassessed 5 years later (Y19) along with the Modified Mini-Mental State Exam. We examined cross-sectional and longitudinal associations between CAC and cognition among 1931 participants using linear and logistic regression. In unadjusted analyses, compared with no calcification, CAC score >300 was associated with decreased performance on all cognitive tests at Y14 in both sexes. Additionally, CAC >300 was associated with a greater 5-year decline in SEVLT Immediate Recall in both sexes and SEVLT Delayed Recall in women. After adjustment for demographic, genetic, metabolic, vascular, and behavioral covariates, CAC score >300 remained associated with greater decline in only SEVLT Delayed Recall in women. Conclusions In women with prediabetes or diabetes, CAC >300, compared with no calcification, was independently associated with greater decline in verbal memory. Registration information clinicaltrials.gov. Identifier: NCT00038727.

Endoscopic characteristics and high-risk background mucosa factors of early gastric cancer after helicobacter pylori eradication: a single-center retrospective study.

Purpose: Gastric cancer still develops after successful Helicobacter pylori(Hp)eradication. In this study, we aimed to explore the characteristics and risks of mucosal factors. Methods: A total of 139 early gastric cancers (EGC) diagnosed in 133 patients after successful eradication from January 2016 to December 2021 were retrospectively included in the Hp-eradication EGC group and 170 EGCs diagnosed in 158 patients were included in the Hp-positive EGC group. We analyzed the clinical, pathological, and endoscopic characteristics between the two groups to identify the features of EGC after Hp eradication. Another 107 patients with no EGC after Hp eradication were enrolled in a Hp-eradication non-EGC group. The background mucosal factors between the Hp-eradication EGC group and the Hp-eradication non-EGC group were compared to analyze the high-risk background mucosal factors of EGC after eradication. In addition, we divided the EGC group after Hp eradication into IIc type and non-IIc type according to endoscopic gross classification to assess the high-risk background factors of IIc-type EGC after Hp eradication. Results: The endoscopic features of EGC after Hp eradication included location in the lower part of the stomach (p=0.001), yellowish color (p= 0.031), and smaller size (p=0.001). The moderate/severe gastric atrophy (GA), intestinal metaplasia (IM) in the corpus, severe diffuse redness, and map-like redness were risk factors for EGC after eradication (p=0.001, p=0.001, p=0.001, and p= 0.005, respectively). The Kyoto classification total score in the EGC group was higher than the non-EGC group (4 vs.3 p<0.001). A multivariate analysis revealed that depressed erosion (OR=3.42, 95% CI 1.35-8.65, p= 0.009) was an independent risk factor for IIc-type EGC after Hp eradication. Conclusion: EGC after eradication are smaller and yellowish lesions located in the lower part of the stomach. The risk background mucosal factors include moderate/severe GA, IM in the corpus, severe diffuse redness, and map-like redness. The Kyoto classification total score of 4 or more after successful eradication treatment might indicate EGC risk. In addition, the IIc-type EGC should be cautioned in the presence of depressed erosion after Hp eradication.

Efficacy and safety of epigallocatechin-3-gallate in treatment acute severe dermatitis in patients with cancer receiving radiotherapy: a phase I clinical trial.

To evaluate the safety and effectiveness of epigallocatechin-3-gallate (EGCG) solution treating the acute severe dermatitis in patients receiving radiotherapy. This phase I research enrolled patients with thoracic cancer receiving radiotherapy at Shandong Cancer Hospital and Institute in Shandong, China. EGCG solution was sprayed to the radiation field when grade III radiation-induced dermatitis (RID) first appearance. EGCG concentration escalated from 660 to 2574 µmol/L using modified-Fibonacci dose-escalation. RID and related symptoms were followed up every day. Between March 2021 and November 2021, 19 patients were enrolled in this phase I research. The median dose of grade III RID first observation was 44 Gy (30.6-52 Gy). As the EGCG treatment was performed continuously, all these grade III RID reactions were significantly decreased to grade I or grade II RID at three days after use of EGCG (p < 0.001). Significant relief can be observed in burning sensation (p < 0.001), tractive sensation (p < 0.001), tenderness (p < 0.001), erythema (p < 0.001), itching (p < 0.001) and pain (p < 0.001) after 15 days of EGCG treatment. No radiation therapy delay or interruption for all 19 patients. No adverse events were observed and reported associated with EGCG. The highest dose of this Phase I trial (2574 µmol/L) was recommended for continuous Phase II trial for further evaluation. In this phase I clinical research, use of EGCG solution is safe and can significantly relief grade III RID in patients receiving radiotherapy. Thus, EGCG might be a new choice for acute sever RID.Trial Registration: ClinicalTrials.gov Identifier: NCT02580279 (Full date of first registration: 12/2014).

Bacillus sp. YC7 from intestines of Lasioderma serricorne degrades nicotine due to nicotine dehydrogenase.

A large number of nicotine-containing wastes produced during the tobacco manufacturing process are seriously harmful to the environment and human health. The degradation and transformation of nicotine-containing environmental contaminants to harmless substances has become an urgent requirement. Lasioderma serricorne can grow and reproduce in nicotine-rich sources, and their intestinal microbiota show promising potential to degrade and utilize nicotine. The purpose of this study is to screen and identify nicotine-degrading bacteria from the intestines of L. serricorne and explore their degradation characteristics. A dominant strain, YC7, with significant nicotine degradation capabilities was isolated from the intestines of L. serricorne. The strain was identified as Bacillus using a polyphasic approach. The test results showed it can produce multiple enzymes that include ß-glucosidase, cellulase, proteases, and amylases. The nicotine-degrading bacteria were functionally annotated using databases. Nicotine dehydrogenase (NDH) was found by combining an activity tracking test and protein mass spectrometry analysis. The YC-7 NDH in the pathway was molecularly docked and functionally verified via the gene knockdown method. The binding ability of nicotine to nicotine-degrading enzymes was investigated using molecular docking. A high-efficiency nicotine-degrading bacteria, YC-7, was isolated and screened from tobacco, and the gene functions related to degradation were verified. This investigation provides a new hypothesis for screening nicotine-degrading bacteria and increases our knowledge of potential nicotine-degrading microbial sources.

Characteristic analysis of early gastric cancer after Helicobacter pylori eradication: a multicenter retrospective propensity score-matched study.

BACKGROUND: Helicobacter pylori (H. pylori) is recognized as a type I carcinogen in gastric cancer (GC). However, GC still occurs after H. pylori eradication, and its diagnosis is more complicated. This study aimed to summarize the characteristics of early GC (EGC) after H. pylori eradication to help accurately identify EGC and avoid missed diagnosis and misdiagnosis. METHODS: A total of 81 patients of EGC after H. pylori eradication (Hp-eradicated group), resected by endoscopic submucosal dissection (ESD), and 105 cases of H. pylori infection-related EGC (control group) were assessed. After propensity-score matching, the clinical characteristics, endoscopic manifestations, and histopathological features of the 62 matched patients in each group were analyzed. We also conducted specific analyses in combination with endoscopic and histopathological images. RESULTS: There were more patients in the Hp-eradicated group who received proton pump inhibitor (PPI) for >1 year compared to the control group (p < 0.001). More patients at OLGA stages I-II before the diagnosis of EGC were in the control group (p = 0.045), especially at stage II. The mucosa in the Hp-eradicated group showed more moderate-to-severe atrophy (p = 0.047), map-like redness (p < 0.001) and mild activity (p < 0.001). The predominant histopathological types differed between the two groups (p < 0.001), and the majority of cases in the Hp-eradicated group were high-grade intraepithelial neoplasia (HGIN). Ki-67 expression was lower in the Hp-eradicated group (p = 0.025). But different eradication intervals of H. pylori have little effect on the characteristics of EGC. Furthermore, PPI uses for >1 year (p = 0.005), mucosal map-like redness (p < 0.001), moderate mucosal atrophy (p = 0.017), and mild activity of gastric mucosa (p = 0.005) were independent characteristics of EGC after H. pylori eradication. CONCLUSION: Our multicenter study revealed that EGC after H. pylori eradication was characterized by long-term PPI use, moderate mucosal atrophy, mucosal map-like redness, the mild activity of gastric mucosa, a higher proportion of HGIN cases, and lower levels of Ki-67.

EGC after H. pylori eradication was characterized by long-term PPI use, moderate mucosal atrophy, mucosal map-like redness, mild activity of gastric mucosa, a higher proportion of HGIN cases, and lower levels of Ki-67.H. pylori-positive patients at OLGA stages I-II are also more likely to progress to EGC.According to the current data, different eradication intervals of H. pylori have little effect on the characteristics of EGC.

Efficacy, safety, and palatability of arpraziquantel (L-praziquantel) orodispersible tablets in children aged 3 months to 6 years infected with Schistosoma in Côte d'Ivoire and Kenya: an open-label, partly randomised, phase 3 trial.

BACKGROUND: WHO has underlined the need for a child-friendly treatment for schistosomiasis, a prevalent parasitic disease in low-income and middle-income countries. After successful phase 1 and 2 trials, we aimed to evaluate the efficacy, safety, palatability, and pharmacokinetics of arpraziquantel (L-praziquantel) orodispersible tablets for preschool-aged children. METHODS: This open-label, partly randomised, phase 3 study was conducted at two hospitals in Côte d'Ivoire and Kenya. Children with a minimum bodyweight of 5 kg in those aged 3 months to 2 years and 8 kg in those aged 2-6 years were eligible. In cohort 1, participants aged 4-6 years infected with Schistosoma mansoni were randomly assigned (2:1) to receive a single dose of oral arpraziquantel 50 mg/kg (cohort 1a) or oral praziquantel 40 mg/kg (cohort 1b) using a computer-generated randomisation list. Cohorts 2 (aged 2-3 years) and 3 (aged 3 months to 2 years) infected with S mansoni, and the first 30 participants in cohort 4a (aged 3 months to 6 years) infected with Schistosoma haematobium, received a single dose of oral arpraziquantel 50 mg/kg. After follow-up assessments, arpraziquantel was increased to 60 mg/kg (cohort 4b). Laboratory personnel were masked to the treatment group, screening, and baseline values. S mansoni was detected using a point-of-care circulating cathodic antigen urine cassette test and confirmed using the Kato-Katz method. The primary efficacy endpoint was clinical cure rate at 17-21 days after treatment in cohorts 1a and 1b, measured in the modified intention-to-treat population and calculated using the Clopper-Pearson method. This study is registered with ClinicalTrials.gov, NCT03845140. FINDINGS: Between Sept 2, 2019, and Aug 7, 2021, 2663 participants were prescreened and 326 were diagnosed with S mansoni or S haematobium. 288 were enrolled (n=100 in cohort 1a, n=50 in cohort 1b, n=30 in cohort 2, n=18 in cohort 3, n=30 in cohort 4a, and n=60 in cohort 4b), but eight participants received antimalarial drugs and were excluded from the efficacy analyses. The median age was 5·1 years (IQR 4·1-6·0) and 132 (47%) of 280 participants were female and 148 (53%) were male. Cure rates with arpraziquantel were similar to those with praziquantel (87·8% [95% CI 79·6-93·5] in cohort 1a vs 81·3% [67·4-91·1] in cohort 1b). No safety concerns were identified during the study. The most common drug-related treatment-emergent adverse events were abdominal pain (41 [14%] of 288 participants), diarrhoea (27 [9%]), vomiting (16 [6%]), and somnolence (21 [7%]). INTERPRETATION: Arpraziquantel, a first-line orodispersible tablet, showed high efficacy and favourable safety in preschool-aged children with schistosomiasis. FUNDING: The Global Health Innovative Technology Fund, the European and Developing Countries Clinical Trials Partnership, and the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945).

Diagnosis and treatment of gastric hamartomatous inverted polyp (GHIP) by endoscopic submucosal dissection: A case report.

RATIONALE: Gastric hamartomatous inverted polyps (GHIP) is not a common disease, and it has rarely been reported in the literature. Preoperative diagnosis is difficult due to the deep position and surface covered with normal gastric mucosa. However, with the progress of endoscopic technology, endoscopic submucosal dissection (ESD) can play a crucial role in the diagnosis and treatment of GHIP. PATIENT CONCERNS: A 61-year-old Chinese man underwent gastroscopy due to abdominal pain 2 months prior that revealed chronic superficial nonatrophic gastritis with erosion and a submucosal tumor in the gastric body (an ultrasound gastroscopy was recommended). Therefore, he was admitted to our hospital for further diagnosis and treatment. DIAGNOSES: A hemispherical submucosal tumor was found in the middle segment of the stomach, with a size of approximately 30 mm × 35 mm and a smooth surface without central ulceration or mucosal bridge formation. Ultrasound gastroscopy showed that the lesion was a hypoechoic mass with uniform internal echo originating from the muscularis propria. INTERVENTIONS: The tumor was completely removed by using ESD. The postoperative pathological results indicated a monocystic structure in the submucosa that was not connected with the surface mucosa. The surface of the cyst was covered with foveolar cells and mucous-neck cells (part of which had low-grade intraepithelial neoplasia), and GHIP was considered to be diagnosed. OUTCOMES: According to the abovementioned endoscopic and pathological features, the patient was finally diagnosed with GHIP. The patient was successfully discharged after surgery and received regular follow-up observations. LESSONS: GHIP is located in the submucosa layer and has the potential risk of malignant transformation. However, it is not easy to diagnose by using gastroscopy and ultrasound gastroscopy. ESD can obtain complete specimens, which contributes to the diagnosis and treatment of GHIP.

Radiotherapy-induced tumor physical microenvironment remodeling to overcome immunotherapy resistance.

The clinical benefits of immunotherapy are proven in many cancers, but a significant number of patients do not respond well to immunotherapy. The tumor physical microenvironment (TpME) has recently been shown to affect the growth, metastasis and treatment of solid tumors. The tumor microenvironment (TME) has unique physical hallmarks: 1) unique tissue microarchitecture, 2) increased stiffness, 3) elevated solid stress, and 4) elevated interstitial fluid pressure (IFP), which contribute to tumor progression and immunotherapy resistance in a variety of ways. Radiotherapy, a traditional and powerful treatment, can remodel the matrix and blood flow associated with the tumor to improve the response rate of immune checkpoint inhibitors (ICIs) to a certain extent. Herein, we first review the recent research advances on the physical properties of the TME and then explain how TpME is involved in immunotherapy resistance. Finally, we discuss how radiotherapy can remodel TpME to overcome immunotherapy resistance.

Characteristics and background mucosa status of early gastric cancer after Helicobacter pylori eradication: A narrative review.

Helicobacter pylori (H pylori) eradication treatment can reduce the risk of gastric cancer. However, early gastric cancer (EGC) can still be detected after eradication. Meanwhile, EGC after eradication is challenging to diagnose by an endoscopist in some cases due to the lack of apparent characteristics and the complex mucosal status. This review aims to summarize the endoscopic and histological characteristics and the mucosal risk factors for gastric cancer after H pylori eradication. The literature was searched for possible reported gastric cancer after eradication in "PubMed." These included related clinical studies and reviews, and unrelated or non-English articles were excluded. Endoscopically, EGC displays a small, reddish and depressed lesion, indistinct border, "gastritis-like" appearance and submucosal invasion. Histologically, it is divided into surface differentiation, nontumorous epithelium, and intestinal type. The risk factors include severe gastric atrophy, intestinal metaplasia in the corpus, and map-like redness. In conclusion, these studies on the characteristics and risk mucosal factors of patients with gastric cancer after H pylori eradication will drive the establishment of a novel endoscopic surveillance and diagnosis system for H pylori-eradicated patients.

Oxaliplatin Induces Immunogenic Cell Death in Human and Murine Laryngeal Cancer.

Background: Cisplatin resistance is observed in patients with laryngeal cancer. The present study was designed to explore the efficacy of oxaliplatin on laryngeal cancer and elucidate the underlying mechanisms. Methods: Cell viability was determined by using MTT assays. Cell apoptosis was determined by using annexin V and propidium iodide (PI) staining. Flow cytometry and immunofluorescence were applied to determine the levels of calreticulin (CALR) and DiD (1,1-dioctadecyl-3,3,3,3-tetramethylindodicarbocyanine). Flow cytometry was applied to analyze the levels of CD83, CD86, IFN-γ-producing CD8+ T cells, and CD4+CD25+FoxP3+ Tregs. The levels of adenosine triphosphate (ATP) were determined by using a chemiluminescent ATP kit and cytokines were determined by using specific enzyme-linked immunosorbent assays (ELISAs). The levels of HMGB1 were determined by using Western blot and ELISA, respectively. The xenograft animal model was constructed to evaluate the antitumor effects of oxaliplatin. Results: Oxaliplatin inhibited cell growth, promoted cell apoptosis, and induced the levels of CALR, ATP, and high mobility group box protein 1 (HMGB1) in Hep-2 cells. Oxaliplatin-treated Hep-2 cells increased the intensity of DiD and the levels of CD83 and CD86 in dendritic cells (DCs), as well as induced the supernatant IL-6 and TNF-α. Oxaliplatin-treated primary laryngeal cancer cell-pulsed DCs increased the IFN-γ-producing CD8+ T cells and suppressed CD4+CD25+FoxP3+ Tregs. In vivo data showed that oxaliplatin suppressed tumor growth and increased the populations of CD86+CD80+ and CD8+CD45+ cells in the tumor tissues. Conclusion: Treatment with oxaliplatin inhibited laryngeal cancer cells by inducing immunogenic cell death.

Comprehensive Analysis of LINC01615 in Head and Neck Squamous Cell Carcinoma: A Hub Biomarker Identified by Machine Learning and Experimental Validation.

Background: Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers, but in clinical practice, the lack of precise biomarkers often results in an advanced diagnosis. Hence, it is crucial to explore novel biomarkers to improve the clinical outcome of HNSCC patients. Methods: We downloaded RNA-seq data consisting of 502 HNSCC tissues and 44 normal tissues from the TCGA database, and lncRNA genomic sequence information was downloaded from the GENECODE database for annotating lncRNA expression profiles. We used Cox regression analysis to screen prognostic lncRNAs, the threshold as HR >1 and p value <0.05. Subsequently, three survival outcomes (overall survival, progress-free interval, and disease-specific survival)-related lncRNAs overlapped to get the common lncRNAs. The hub biomarker was identified using LASSO and random forest models. Subsequently, we used a variety of statistical methods to validate the prognostic ability of the hub marker. In addition, Spearman correlation analysis between the hub marker expression and genomic heterogeneity was conducted, such as instability (MSI), homologous recombination deficiency (HRD), and tumor mutational burden (TMB). Finally, we used enrichment analysis, ssGSEA, and ESTIMATE algorithms to explore the changes in the underlying immune-related pathway and function. Finally, the MTT assay and transwell assay were performed to determine the effect of LINC01615 silencing on tumor cell proliferation, invasion, and migration. Results: Cox regression analysis revealed 133 lncRNAs with multiple prognostic significance. The machine learning algorithm screened out the hub lncRNA with the highest importance in the RF model: LINC01615. Clinical correlation analysis revealed that the LINC01615 increased with increasing the T stage, N stage, pathology grade, and clinical stage. LINC01615 could be used as a predictor of HNSCC prognosis validating by a variety of statistical methods. Subsequently, when clinical indicators were combined with the LINC01615 expression, the visualization model (nomogram) was more applicable to clinical practice. Finally, immune algorithms indicated that LINC01615 may be involved in the regulation of lymphocyte recruitment and immunological infiltration in HNSCC, and the LINC01615 expression represented genomic heterogeneity in pan-cancer. Functionally, silencing of LINC01615 suppresses cell proliferation, invasion, and migration in HEP-2 and TU212 cells. Conclusion: LINC01615 may play an important role in the prostromal cell enrichment and immunosuppressive state and serve as a prognostic biomarker in HNSCC.